1. Field of the Invention
The present invention relates to erythromycin A derivatives and the method for the preparation of the same.
2. Description of the Prior Art
6-O-Methylerythromycins are useful as anti-bacterial agents or intermediates for synthesis of the antibacterial agents. For example, 6-O-methylerythromycin A is not only stable under the acidic conditions but also has a strong antibacterial activity when compared with erythromycin A. Especially, this compound shows an excellent effect for treatment of infections by oral administration, and therefore it is a useful antibacterial agent.
There are known in the past some methods for methylating the hydroxy group at the 6-position of the erythromycin A derivatives, for example, (1) a method which comprises substituting the hydrogen atom of the hydroxy group at the 2′-position and the methyl group of the dimethylamino group at the 3′-position of the erythromycin A derivatives by benzyloxycarbonyl groups, and then methylating the resulting compound (U.S. Pat. No. 4,331,803), and (2) a method which comprises converting erythromycin A derivatives having the protected hydroxy group at the 2′-position and/or the protected dimethylamino group at the 3′-position into the various kind of the substituted oxime derivative, and then methylating the substituted derivatives (European Patent 158,467).
However, since erythromycin A has many hydroxy groups, there are obtained various kind of erythromycin A derivatives which are methylated at hydroxy groups at any other than the 6-position as the by-products by the method of item (1). Accordingly, this method requires the complicated procedure for purification of the 6-O-methylerythromycin A derivatives, and has drawback of causing low yield of said derivatives. Although it is possible to methylate selectively the 6-hydroxy group by the method of item (2), when the erythromycin A 9-oxime derivative whose 2′-hydroxy group only is protected is methylated, the 3′-dimethylamino group is changed to a methyl quaternary salt under ordinary methylation conditions. Furthermore it is difficult to return the salt to a dimethylamino group, accordingly, it is necessary to protect both of the 2′-hydroxy group and 3′-dimethylamino group for the practical preparation method.